FK409, a spontaneous nitric oxide releaser, attenuates allograft vasculopathy in a rat aortic transplant model

Johji Fukada, Stefano Schena, Ivan Tack, Phillip Ruiz, Yoshihiko Kurimoto, Manhui Pang, Abdelouahab Aitouche, Tomio Abe, Liliane J. Striker, Si M. Pham

Research output: Contribution to journalArticlepeer-review

Abstract

Although systemic administration of NO donors has been shown to attenuate the development of neointimal hyperplasia in the balloon injury model, this strategy has not been tested in a model of allograft vasculopathy. In this study, we investigated the effect of FK409, a spontaneous NO releaser, on the development of allograft vasculopathy, using a rat aortic transplant model. Thoracic aortas from ACI rats were transplanted heterotopically into the abdominal aorta of Wistar-Furth rats. Postoperatively, recipients received FK409 orally every 8 hours from the day of transplantation to the time of euthanization. Morphometric and immunohistochemical analyses were performed on the aortic grafts 8 weeks after transplantation. Control allografts showed severe neointimal hyperplasia, which consists mainly of α-actin-containing vascular smooth muscle cells. The FK409-treated allografts showed a dose-dependent reduction (statistically significant compared with the control) in the neointimal thickness as the dose increased from 1 to 10 mg/kg (thrice per day). However, there was no significant difference in the neointimal thickness between groups treated with 10 and with 20 mg/kg. FK409 treatment (10 mg/kg) caused a significant decrease in DNA synthesis (5-bromo-2-deoxyuridine [BrdU] uptake), an increase in DNA fragmentation (terminal deoxynucleotidyltransferase-mediated uridine nick-end labeling [TUNEL]), and upregulation of Fas expression, in the neointimal vascular smooth muscle cells. These data suggest that FK409 attenuates the allograft vasculopathy in a rat aortic transplant model.

Original languageEnglish (US)
Pages (from-to)66-72
Number of pages7
JournalCirculation research
Volume87
Issue number1
DOIs
StatePublished - Jul 7 2000

Keywords

  • Allograft
  • Apoptosis
  • FK409
  • Fas
  • In situ nick-end labeling

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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